B cell activating factor (BAFF) levels are associated with failed remission after 12 months of treatment with benralizumab and mepolizumab in severe asthma

Abstract The introduction of biologicals interfering with the interleukin-5 (IL-5) pathway has revolutionized the treatment of severe eosinophilic asthma (SEA), rendering remission an achievable goal even in patients with previously uncontrolled disease. This study investigated whether specific plasma biomarkers or clinical features could predict clinical remission in patients treated with an IL-5- (mepolizumab) or IL-5 receptor alpha-antibody (benralizumab) for severe eosinophilic asthma. Clinical remission, defined as sustained symptom control, absence of exacerbations, stable lung function, and no need for systemic corticosteroids, was assessed after 12 months. Plasma levels of 30 cytokines and chemokines were measured at baseline and after three months in 41 patients receiving either mepolizumab or benralizumab. Twelve patients (29%) achieved remission. Clinical characteristics and commonly used biomarkers, including blood eosinophil counts and fractional exhaled nitric oxide, showed no significant association with remission. However, elevated levels of B cell–activating factor (BAFF) at baseline and 3 months follow-up were significantly associated with failure to achieve remission. Logistic regression analyses revealed that plasma BAFF levels were predictive for remission status outperforming conventional eosinophilic inflammation markers. These findings suggest that elevated plasma BAFF may indicate B cell–driven inflammatory in severe eosinophilic asthma, which is not adequately addressed by therapies targeting interleukin-5. BAFF may serve as a valuable biomarker to identify patients less likely to respond to interleukin-5–directed treatments and who may benefit from alternative therapies. Further research is needed to validate these findings and explore the role of BAFF in personalized treatment strategies for severe asthma.